Ultra-high resolution mass spectrometry, such as is achievable using a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS), or an Orbitrap™ mass spectrometer, enables the identification of thousands of different molecular formulas in organic matter. Coupled with liquid chromatography (LC), accurate mass determination of components of complex mixtures can be made on a routine basis. Applications include, amongst others, screening combinatorial chemistry libraries and identifying metabolites related to drug discovery, screening for anabolic steroids in illegal cocktails and fungal metabolites in culture extracts, and elucidating unknown compounds in environmental water.
The output from the mass spectrometer must be interpreted before samples can be characterised, and this presents technical problems. Molecular formula assignment from mass data is most critical and time-consuming. Accurate mass measurement by mass spectrometry is a common technique to determine elemental composition, facilitated by ultra high resolution mass spectrometers. Despite technological advances and improved mass accuracy, often the mass accuracy alone does not provide unequivocal identification. In many cases, several different structural formulae can be identified for the same molecular mass. The number of candidate formulae increases exponentially with mass, making high mass molecular determination particularly challenging. Therefore, automated procedures are required for an efficient exploitation of the extensive data sets produced by mass spectrometry, when characterising samples.
Various methods of determining the elemental composition of molecular mass peaks have been proposed, yet there remains a need for a method that produces results of higher specificity and accuracy. Other workers have reported the use of the accurate mass of measured peaks together with the relative isotopic abundances in order to identify the elemental composition of molecular peaks measured by high resolution mass spectrometry, see for example Breitling, R.: Pitt, A. R. & Barrett, M. P. “Precision mapping of the metabolome”, Trends in Biotechnology, 2006, 24, 543-548; Boecker, S.; Letzel, M.; Liptak, Z. & Pervukhin, A. “Decomposing Metabolomic Isotope Patterns”, Algorithms in Bioinformatics, 2006, 12-23; and, Grange, A. H.; Winnik, W.; Ferguson, P. L. & Sovocool, G. W. “Using a triple-quadrupole mass spectrometer in accurate mass mode and an ion correlation program to identify compounds”, Rapid Communications in Mass Spectrometry, 2005, 19, 2699-2715.